Exam 2 lecture 3 Flashcards
Name the gram positive antibiotics
Vancomycin
Quinupristine-dalfopristine
Linezolid
Tedizolid
Daptomycin
Telavancin
Dalbavancin
Oritavancin
Why has the use of vancommycin increased over the past decades
Due to the emergence of MRSA and PRSP
What does the large structure of vanc entail
Cant be absorbed orally
Cant get into CNS
Does not get removed by hemodialysis membrane
These are common to the otehrs aswell
Vancomycin MOA? bacteriostatic/bactericidal?
Inhibits cell wall synthesis at site different than B lactams
It inhibits synthesis and assembly of second stage of cell wall synthesis by binding to D ala D ala on cell wall and preventing cross linking
Time dependent bactericidal activity, slowly kills bacteria (static against enterococcus)
How fast/slow is vanc
SLOWEST DRUG is vanc
Mechanism of resistance of vanc
- Resistance in VRE and VRSA is due to modification of D ala D ala binding site of peptidoglycan. D ala replaced by D lactate. Led to loss of critical H bond and loss of antibacterial activity.
- VISA (vancomycin intermediate staph aureus)- They had thickened cell wall
What are the phenotypes that confir resitance to vancomycin (exam)
van A is the most important
Spectrum of activity of vancomycin
Gram positive bacteria (aerobes and some anaerobes)
-Streptococcus (group, viridians, pneumonia) including PRSP*
- MRSA* and MSSA*
- C diff* and clostridium spp
- no activity against gram negatives
What should we use in the case of a serious MSSA infection
B lactam (nafcillin/cefazolin)
Only used vanc if we have to bc it is a slow killer
Vanc is THE drug of choice in what disease
MRSA
What are target organisms for vancomycin
MRSA, MSSA, PRSP and c diff
What is the drug of choice for C diff
Vancomycin (oral)
What group does vancomycin show synergy with? Give an example
Aminoglycoside synergy
Gentamycin + vanc used together
What formulations does vancomycin come in? How is it used
Oral and iV
HORRIBLE oral absorption, but we use this to our advantage to target patients with C diff (collitis)
Important point to know about distrubution of vancomycin
Takes one hour to distrubute form plasma into tissue compartment (take that into account when looking at pak as it will be falseky elevated)
How is vanc eliminated? half life?
Eliminated by kidney
half life depends on renal function
How is hemodialysis going to affect vanc
Removed by hemodialysis (30-40% removed per hemodialysis sessions)
When should the peak be drawn for serum concentration in patients on vanc? trough? Target AUC/MIC?
60 mins after end of infusion (target 30-40)
Trough- prior to next dose (10-15)
Target AUC/MIC= 400-600
clinical uses of vancomycin (exam)
infections due to MRSA (THE DRUG OF CHOICE EXAM)
serious gram positive infection in B lactam allergic patients
PRSP (target organism EXAM)
ORAL vancomycin for C diff collitis (EXAM)
adverse effects of vancomycin (exam)
- Red man syndorme (AKA red neck syndorme)
Related to RATE of IV infusion, no faster than 15 mg per minute
5-15 mins after infusion
Pretreat with antihistamine
We can give it again if we lengethen infusion
- Nephrotoxicity and ototoxicity (rare with monotherapy, more common when administered with other nephro/oto agents)
- Thrombophlebitis, interstitial nephritis
What are some risk factors for nephro/ototoxicity with vancomycin (exam)
IT is reversible
Risk factors- renal impairement, prolonged therapy, high doses, high serum concentrations, use of other nephro/oto toxic agents
What is synercid a combination of? WHat kind of drug was it?
Quinupristine/dalfopristine
It is a streptogramin
What was synercid developed for
developed bc of need for antibiotics with activity aganst resistant gram positive bacteria, namely VRE
ROA synercid? CNS action? Hemodialysis removal
TOO big for oral
No CNS
Not removed by hemodualysis membranes
MOA of synercid? Where does it bind? Bacteriostatic/cidal?
Each agent acts individually on 50S ribosomal unit t inhibit early and late stages of protein synthesis
Binds to 50s ribsosme near site where macrolides and clindamycin bind
bacteriostatic (may be cidal against some bacteria)
Mechanism of resistance of synercid
alteration in ribsosme binding site
Enzymatic inactivation
spectrum of activity of synercid
Gram positive bacteria
-ENterococcus Faecium* ONLY
-PRSP*
-MSSA and MRSA
- Coagulase negative staphylococcus
What is one of the short comings of synercid
ONLY works on VRE enterococcus faecium,
VRE enterococcus Faecallis
is synercid time dependent of concentration dependent? Distribution?
Time dependent bactericidal
MINIMAL CSF PENETRATION
When do we need to adjust synercid
Not in renal but in hepatic
Clinical use of synercid
VRE (faecium) bacterium where we can not use linezolid or daptomycin
drug interactions of synercid (exam)
3A4 inhibitor
HMG CoA reductase (lovastatin, simvastatin, atorvastatin)
cyclosporin
carbamezapine
adverse effects of synercid
Venous irritation (only use central vein) (66%)
Myalgias, arthralgias (22%)
What are oxazolidinone drugs? ROA?
Linezolid and tedizolid
PO and IV
What is the reason they developed linezolid
needed for antibiotics with activity against resistant gram positives (VRE, MRSA, VISA)
also is effective against enterococcus faecium and Faecalis
MOA of linezolid
Bind to 50S ribosomal subunit near surface of 30S subunit (unique binding site). Causes inhibition of 70S initiation complex
Are oxazolidinones bacteriocidal or bacteriostatic
Bacteriostatic (cidal against some)
Mechanism of resistance of oxazolidinones
Alteration in ribosomal binding site (rare)
Cross resistance with protein synthesis inhibitors is unlikely
spectrum of activity of linezolid and tedizolid
Gram positive bacteria
Group, viridians and pneumoniae streptococcus (including PRSP)
- enterococcus faecium AND faecalis (including VRE)
- MSSA, MRSA and VRSA*
For MSSA, what do we use before linezolid? MRSA?
Linezolid is bacteriostatic so we use other drugs before it.
MSSA- nafcillin, cephazolin and Vanc
MRSA- Vancomycin, dapto
What are linezolid and tedizolids oral bioavailability? CSF penetration? eliminated by? Renal adjustment?
91% tedizolid and 100% linezolid
Linezolid CSF penetration= 30%
Removed renally and non renally
No renal adjustments
removed by HD
Clinical use of linezolid/tedizolid
- reserved for serious/complicated infections caused by resistant gram positive bacteria
- VRE bacteremia or UTI
- Nosocomial pneumonia due to MRSA and serious infections due to MRSA
drug interactions of linezolid and tedizolid
Serotonin syndrome with SSRIs/SNRIs
adverse effects of linezolid and tedizolid
Optic and peripheral neuropathy
Thrombocytopenia or anemia
most often with prolonged tx
Name lipopeptide drug? Why was it developed
Daptomycin
Developed bc of the need for antibiotics with activity against VRE, MRSA, VISA
How big/small is daptomycin? How does this affect the ROA? does it get into CSF? Hemodialysis removal?
Huge molecule, not oral
No CSF or HD removal
MOA of daptomycin? Time or concentration dependent? Static or cidal?
Binds to bacteria and inserts lipophilic tail into cell wall to form trans membrane channel. Causes leak of cellular contents.
Concentration dependent bactericidal activity
mechanism of resistance of daptomycin
Rarely reported in VRE and MRSA due to altered cell membrane binding
spectrum of activity of daptomycin
Gram positive
-Group, viridians, pneumo Strep (PRSP)
-Both enterococcus faecium and facialis (including VRE)
- MSSA, MRSA and VRSA*
elimination of daptomycin? Would dosage adjustment be required?
Excreted primarily in kidney
Dosage adjustments required in presence of RI
clinical uses and dosing of dapotmycin? When should it not be used?
Reserved for serious/complicated infections caused by resistant bacteria
6 mg/kg/day
Daptomycin should not be used in tx of pneumonia and left sided endocarditis
adverse effects and drug interactions of daptomycin
-myopathy and CPK elevation <2%
- Acute eosinophilic pneumonia
Drug i/a
- HMG CoA reductase inhibitors (statin) may lead to increased myopathy
Why were lipoglycoeptides developed? What are the drug names?
lipoglycopeptides were developed to address the need for antibiotics with activity against VRE, MRSA, VISA
Televancin
Dalbavancin
Oritavancin
How big/small are lipoglycopeptides? How does this affect ROA? CSF penetration? HD removal?
Huge
Not available orally
Not getting into CSF
Not removed by HD
Mechanism of action of lipoglycopeptides? Time/concentration dependent? Bacteriostatic/cidal?
All 3 interfere with polymerization and cross linking of peptidoglycan by binding D ala D ala
Televancin and oritavancin can bind to bacterial membranes and insert lipophilic tail to form transmembrane channel. leakage.
COncentration dependent bacteriocidal activity
mechanism of resistance of lipoglycopeptides (televancin oritavancin dalbavancin)
Alteration in peptidoglycan terminus (oritavancin still maintains activity)
Spectrum of activity of lipoglycopeptides
Gram positive
- group, viridians and pneumoniae strep
Enterococcus AND faecalis *
MSSA, MRSA and VISA*
Some strains of enterococcus faecalis and faecium are resistant to which lipoglycopeptides
televancin and dalbavancin
How are lipoglycopeptides eliminated? Which ones need dosage adjustments and which ones dont?
Televancin- excreted by kidneys. Dosage adjustment needed
Dalbavancin- 33% unchanged in urine, dosage adjustment needed
Oritavancin- ONLY ONE no adjustment needed
clinical uses of lipoglycopeptide
serious/complicated infections caused by resistant bacteria
What are some interactions lipoglycopeptides have?
Televancin and oritavancin interfere with coagulation tests (PT, INR, aPTT) by binding to artificial phospholipid surfaces
Adverse effects of lipoglycopeptides? Black box?
Televancin- Nephrotoxicity, QTc prolongation, taste disturbances
All- Infusion related rxn (red man)
Televancin black box warning on use during pregnancy.
What is drug of choice for unfections due to MRSA
Vancomycin
